Catalytic Radical-Polar Crossover Ritter Reaction

Abstract

A catalytic radical-polar crossover Ritter reaction is described. The transformation proceeds under acid-free conditions and tolerates a variety of functional groups. The catalyst design overcomes limitations in the substitution pattern of starting materials and enables hydroamidation of a diverse range of alkenes. Formation of hydrogen contributes to the background consumption of reductant and oxidant and competes with the desired pathway, pointing to a mechanistic link between hydrogen atom transfer-initiated organic reactions and hydrogen evolution catalysis.

Electrocatalytic Radical-Polar Crossover Hydroetherification of Alkenes with Phenols

“…A variety of functional groups including methoxyarene (40), sulfonamide (41), silyl protected alcohol (42), thiophenyl ester (43) or even fructose derivative (44) smoothly participated the reaction without difficulty. This hydroetherification method also proved efficient in engaging styrenes as substrates, which are considered to be more challenging due to the unfavorable homocoupling or reduction caused by intrinsically high stability of benzylic radicals generated by cage-escape mechanism (vide supra, Fig.…”

“…[33][34][35][36][37][38] These methods however involve the use of chemical oxidants with minimal control over the oxidizing potential that dictates the bimetallic catalyst-controlled oxidation, [39] which consequently necessitates the use of solvent amounts of nucleophiles to engage with unactivated multisubstituted alkenes. [40][41][42] Thus, the development of a new catalytic strategy that allows proficient and controllable generation of carbocations from the corresponding alkenes remains a major challenge for hydrofunctionalization with important but challenging nucleophiles such as phenols. [43][44] Herein we report a cobalt-catalyzed electrochemical radical polar crossover hydroetherification of alkenes in which a controllable electricity drives systematic consecutive oxidations of cobalt catalyst to generate carbocationic species from a comprehensive class of olefins, which would subsequently be entrapped by phenols to afford the desired alkyl aryl ethers (Fig.…”

Electrocatalytic Radical-Polar Crossover Hydroetherification of Alkenes with Phenols

“…[37][38][39][40][41][42] These methods however involve the use of chemical oxidants with minimal control over the oxidizing potential that dictates the bimetallic catalyst-controlled oxidation, [43] which consequently necessitates the use of solvent amounts of nucleophiles to engage with unactivated multisubstituted alkenes. [44][45][46] In addition, this rate-determining bimetallic disproportionation (k2) often deteriorates the desired nucleophilic entrapment particularly when weak nucleophiles are employed. This is mainly due to solvent cage escape process (k1) leading to the formation of solvent-separated radicals, which can irreversibly be driven to unwanted side reactions (Figure 1C, middle part).…”

“…Products 40 and 41, only containing a simple alkyl chain, were afforded in excellent yields. A variety of functional groups including methoxyarene (42), sulfonamide (43), silyl protected alcohol (44), thiophenyl ester (45) or even fructose derivative (46) smoothly participated the reaction without difficulty.…”

“…Ultimately, these results support our voltametric studies (Figure 2C) in proving the quasi-reversible feature of second redox wave, in which the erosion of reversibility originates in the irreversible cage escape to generate free carbocation. [44][45][46] In summary, we present a modular approach to synthesizing alkyl aryl ethers by integrating a wide range of alkenes and phenols. This protocol involves successive oxidative SET reactions to enable conventional radical polar crossover reactions to allow direct entrapment of cationic alkyl intermediates by challenging nucleophilic phenols.…”